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Fungal Meningitis

Fungal Meningitides

Fungal meningitis refers to meningitis caused due to a fungal infection.


Presentation

The clinical features of fungal meningitis similar to any other cause of meningitis. It can present with fever, neck stiffness, nausea, photophobia, vomiting, headache and mental status changes [5] [6]. Fungal meningitis is non-contagious as compared to bacterial and viral meningitis that are known to be contagious. Fungal meningitis can occur only due to hematogenous or contiguous spread from a local site of infection to the CNS [5] [6]. It is typically found in immunocompromised hosts, although the causitive pathogen can vary according to the local environment [6] [7].

Clinical features of fungal meningitis are indistinguishable from other causes of meningitis and hence require various laboratory tests to obtain a diagnosis. The presenting signs and symptoms may consist of the following:

Fever
  • These include headache, nausea, vomiting, stiffness of the neck, fever and inability to tolerate bright light.[symptoma.com]
  • School Exclusion Criteria Children with fungal meningitis should be kept out of school or childcare until they are fever free for 24 hours without the use of fever suppressing medications.[dshs.state.tx.us]
  • For 2 cases, fever and meningeal signs were absent at presentation. Patients with fungal meningitis may present with ischemic stroke detected on initial imaging scans. A definitive diagnosis should not delay early antifungal treatment.[ncbi.nlm.nih.gov]
  • Valley Fever and Pregnant Women. State of California Health and Human Services Agency . January 2016. Valley Fever Statistics. CDC . November 9, 2017. Thomas M. The Mysterious Fungus Infecting the American Southwest. The Atlantic . August 8, 2014.[everydayhealth.com]
  • You have a headache, fever, and stiff neck. You are confused. When should I contact my healthcare provider? You have a fever. You have questions or concerns about your condition or care. Care Agreement You have the right to help plan your care.[drugs.com]
Fatigue
  • We ask about general symptoms (anxious mood, depressed mood, fatigue, pain, and stress) regardless of condition. Last updated: January 31, 2019[patientslikeme.com]
  • Two weeks later, at a home visit conducted by the Virginia health department, his only symptom was fatigue. " Exserohilum meningitis is a new clinical entity," Smith and colleagues noted, so "it is not known whether the current treatment guidance is sufficient[medpagetoday.com]
  • She’d been treated for neck pain and a chronic condition called fibromyalgia that is defined by aches and pains all over the body and general weakness and fatigue.[vitals.nbcnews.com]
  • At a home visit conducted by the health department 2 weeks later, the patient reported only fatigue.[nejm.org]
Candidiasis
  • Cryptococcal meningitis and candidiasis patients accrued the largest average charges ( 103 236 and 103 803, respectively) and spent the most time in the hospital on average (70.6 and 79 days).[ncbi.nlm.nih.gov]
  • Candidiasis is usually acquired in an inpatient setting. The route of transmission for most fungal infections is usually thorough inhalation of spores. Meningitis occurs when the fungal infection spreads to the brain.[symptoma.com]
  • Guidelines for Treatment of Candidiasis. Clinical Infectious Diseases . January 15, 2004. Perfect JR, Dismukes WE, Dromer F, et al.[everydayhealth.com]
  • Yeast Infections Yeast infections of the skin are called cutaneous candidiasis and are caused by yeast-like fungi called candida. They occur when yeast on the skin grows more actively and causes a red, scaling, itchy rash on the skin.[m.webmd.com]
Malaise
  • Clinical features May be associated with features of pneumonia More appropriately termed meningoencephalitis as brain parenchyma is also involved Onset over several weeks: headache fever malaise altered mental status Clinical signs often absent but may[aic.cuhk.edu.hk]
Overeating
  • We studied the largest and most diverse group of fungal meningitis patients to date, over the longest follow-up period, to examine the broad impact on resource utilization within the United States.[ncbi.nlm.nih.gov]
  • (NaturalNews) In what's being called the "biggest criminal case ever brought in the U.S. over contaminated medicine," U.S.[naturalnews.com]
  • […] opinion A final settlement has been reached in the 2012 fungal meningitis outbreak that killed 64 people and sickened over 750.[livingstondaily.com]
Painful Ophthalmoplegia
  • Fungal meningitis caused by a Malassezia species masquerading as painful ophthalmoplegia. Clin Neurol (Tokyo). 1993; 33 462 41 Watanabe S, Hironaga M. An atypical isolate of Scedoporium apiospermum from a purulent meningitis in man.[doi.org]
Hearing Impairment
  • Possible after-effects/resulting disabilities: Physical/specific hearing impairments/deafness/tinnitus loss of sight/changes in eyesight (not necessarily permanent) brain damage (severe damage only occurs in 2% of cases) stiffness in joints loss of balance[deafblind.com]
Headache
  • A week later, she developed the severe headache – so bad it drove her to the ER. Now, of course, doctors know that anyone who has had a steroid injection and shows up with symptoms like a severe headache should be checked for infection.[vitals.nbcnews.com]
  • These include headache, nausea, vomiting, stiffness of the neck, fever and inability to tolerate bright light.[symptoma.com]
  • Early symptoms of fungal meningitis, such as headache, fever, dizziness, nausea and slurred speech, are subtler than those of bacterial meningitis and can take nearly a month to appear.[abcnews.go.com]
Confusion
  • Symptoms of fungal meningitis are generally similar to those of other types of meningitis, and include: a fever, stiff neck, severe headache, photophobia (sensitivity to light), nausea and vomiting, and altered mental status (drowsiness or confusion).[en.wikipedia.org]
  • You are confused. When should I contact my healthcare provider? You have a fever. You have questions or concerns about your condition or care. Care Agreement You have the right to help plan your care.[drugs.com]
  • Symptoms of meningitis include headache, fever, stiff neck, dizziness, confusion, and even strokes, as well as swelling, redness or discharge from the site of the injection. Get treatment right away for those symptoms.[thefloridafirm.com]
  • Also those with fungal meningitis may also experience, dislike of bright lights, changes in mental status, confusion, hallucinations, and personality changes Those at high risk for fungal meningitis include those who have certain medical conditions like[dshs.state.tx.us]
Neck Stiffness
  • It can present with fever, neck stiffness, nausea, photophobia, vomiting, headache and mental status changes. Fungal meningitis is non-contagious as compared to bacterial and viral meningitis that are known to be contagious.[symptoma.com]
  • “Fever, new or worsening headache, sometimes neck stiffness. We’ve also seen in a few patients signs and symptoms of stroke, sudden onset of slurred speech, dizziness, difficulty walking, sudden weakness.”[learningenglish.voanews.com]
  • See When Neck Stiffness May Mean Meningitis Physicians should actively contact any patient who has recently received the injection to determine if their patients are having any symptoms.[spine-health.com]
  • Signs and Symptoms of Fungal Meningitis Elevated body temperature Headaches Neck stiffness Nausea Vomiting Light sensitivity Mental status alteration Diagnosis for Fungal Meningitis If there is a suspicion of meningitis blood draws are taken and also[epainassist.com]
Altered Mental Status
  • Symptoms of fungal meningitis are generally similar to those of other types of meningitis, and include: a fever, stiff neck, severe headache, photophobia (sensitivity to light), nausea and vomiting, and altered mental status (drowsiness or confusion).[en.wikipedia.org]
  • Clinical features May be associated with features of pneumonia More appropriately termed meningoencephalitis as brain parenchyma is also involved Onset over several weeks: headache fever malaise altered mental status Clinical signs often absent but may[aic.cuhk.edu.hk]
  • Top of Page Signs and Symptoms Signs and symptoms of fungal meningitis may include the following: Fever Headache Stiff neck Nausea and vomiting Photophobia (sensitivity to light) Altered mental status (confusion) Diagnosis If meningitis is suspected,[cdc.gov]
  • A: “Signs and symptoms of fungal meningitis are similar to those of meningitis from other causes and may include the following: headache, fever, sensitivity to light, stiff neck, nausea and vomiting, and altered mental status.[daytondailynews.com]
Stupor
  • Like other forms of meningitis, typical symptoms associated with fungal meningitis include fever and headache, neck stiffness/pain and deterioration of mental status (drowsiness, stupor and coma). Cranial nerve deficits and seizures can also occur.[nervous-system-diseases.com]
  • Corticosteroids ( prednisone or dexamethasone ) may be added if patients present with stupor, coma, or neurologic deficits.[msdmanuals.com]

Workup

For any case with suspected meningitis, blood and cerebrospinal fluid (CSF) samples are sent for laboratory evaluation urgently, since the treatment varies according to the causitive agent. The tests include:

  • Lumbar puncture (LP) and CSF analysis

In fungal meningitis, an elevated opening pressure of CSF during LP has been associated with poor prognosis.

CSF analysis usually exhibit decreased glucose levels, high protein levels and a lymphocytic pleocytosis in the range of 10-200 cells/µl for most fungal causes of meningitis, including Cryptococcosis. Rarely, cases of C. immitis have been associated with eosinophilic pleocytosis.

  • CSF culture, blood culture

These can be used as a mode of obtaining a definitive diagnosis for certain fungal pathogens, such as H. capsulatum, B. dermatitidis, C. immitis and Candida spp.

  • Fungal serology

The detection fungal antigens is frequently used for diagnosing fungal meningitis, especially for histoplasmosis. Serology is helpful for diagnosing the fungi that are difficult to culture. However, in certain cases such as B. dermatitidis, serology is not considered conclusive since a negative test fails to rule out the diagnosis.

Lymphocytopenia
  • Idiopathic CD4 T-lymphocytopenia: four patients with opportunistic infections and no evidence of HIV infection. N Engl J Med. 1993; 328 393 187 Weidenheim K M, Nelson S J, Kure K, Harris C, Biempica L, Dickson D W.[doi.org]
Gram-Positive Bacteria
  • Seventy six were Gram-positive bacteria, 29 were Gram-negative and there were ten fungal isolates.[ncbi.nlm.nih.gov]
Scedosporium
  • We describe a fatal case of meningitis caused by Lomentospora prolificans (which was previously named Scedosporium prolificans), after an allogeneic hematopoietic stem cell transplantation (allo-HSCT).[ncbi.nlm.nih.gov]
Alternaria
  • On a rare disease due to Alternaria tenuis nees Tohoku J Exp Med. 1960; 72 78 32 Pore R S, Chen J. Meningitis caused by Rhodotorula Sabouraudia. 1976; 14 331 33 Huttova M, Kralinsky K, Horn J.[doi.org]
Fonsecaea Pedrosoi
  • Fonsecaea pedrosoi pneumonia and Emericella nidulans cerebral abscesses in a bone marrow transplant patient. Clin Infect Dis. 1995; 21 1346 157 Jamjoom A B, al-Hedaithy S A, Jamjoom Z A. Intracranial mycotic infections in neurosurgical practice.[doi.org]

Treatment

The treatment for fungal meningitis usually consists of high-dose anti-fungal medications administered intravenously (IV) in an inpatient setting. The treatment duration is variable, and depends upon factors such as the immune status of the patient and the pathogen involved [5] [6]. Patients diagnosed with comorbidities such as diabetes, cancer and AIDS that compromise the immune system usually have a prolonged course of treatment [5] [6].

Cryptococcal meningitis

It is known to be an opportunistic infection in individuals diagnosed with HIV/AIDS. Treatment consists of amphotericin B (0.7-1 mg/kg/day IV) for a minimum of 2 weeks. Flucytosine (100mg/kg by mouth in 4 divided doses) can also be added. Liposomal amphotericin B (amphotericin B liposome 3-4 mg/kg/day or amphotericin B lipid complex 5 mg/kg/day) may be considered in cases with predisposition to or pre-existing renal dysfunction. The consolidation phase of the therapy involves administering fluconazole (400 mg/day) for 8 weeks. Itraconazole can be used as an alternative if the patient is not able to tolerate fluconazole. The maintenance phase of the therapy consists of fluconazole 200 mg/day to prevent relapse. Fluconazole is known to be superior to itraconazole and amphoterecin B (1 mg/kg once a week), both, for preventkion of relapse. Cases with HIV/AIDS have a higher risk of relapse.

In places with limited resources, fluconazole and amphotericin B are considered as optimal for treating HIV/AIDS associated acute cryptococcal meningitis. It is recommended that the administration linked to healthcare services in countries with inadequate health facilities should consider providing drugs such as flucytosine that are often unavailable at these places, to optimize HIV treatment programs [8].

Coccidioides immitis

C. immitis associated meningitis is treated with fluconazole (400 mg/day by mouth). Some practitioners prefer initiating the treatment with a higher dose of fluconazole (up to a maximum of 1000 mg/day) or intrathecal amphotericin B and fluconazole combination. The efficacy of itraconazole (400-600 mg/day) is comparable to the aforementioned options. Miconazole IV may also be considered. C. immitis meningitis often requires lifelong treatment.

Histoplasma capsulatum

The preferred option for treating meningitis secondary to H. capsulatum is liposomal amphotericin B, dosage being 5 mg/kg/day IV, with a total of 175 mg/kg over 4-6 weeks). This is followed by a minimum 1 year therapy with itraconazole (200-300 mg BID to TID) till the abnormalities in CSF are resolved and/or histoplasma antigen levels return to normal reference range. The level of itraconazole in blood must be monitored periodically to ensure adequate absorption of the drug. 

Candida species

The drug of choice for the treatment of meningitis due to Candida is amphotericin B (0.7 mg/kg/day). Another drug, flucytosine (25 mg/kg QID, dosage adjusted to obtain serum level of 40-60 µg/ml) is often added to amphotericin B. Suppresive or follow-up therapy usually involves using azoles.

There is a high risk of relapse in candidal meningitis. Treatment is usually continued for four weeks after resolution of symptoms, however, there are no specific guidelines for the duration of the treatment. If candidal meningitis has occured secondary to neurosurgical procedures, removal of any implanted prosthetic materials, such as ventriculoperitoneal shunts, that are suspected of being a nidus for infection should be considered.

Sporothrix schenckii

The best initial therapy is liposomal amphotericin B, and itraconazole (200 mg BID) as a step-down once the patient responds to amphotericin B. The total duration of therapy should be a minimum of 12 months. Itraconazole can also be used as lifelong suppression therapy, but only after initial therapy with amphotericin B. Itraconazole is more effective against S. schenckii that fluconazole.

Exserohilum rostratum

According to the current guidelines from CDC, liposomal amphotericin B or voriconazole IV are the most optimal options for treating E. rostratum [9].

Prognosis

Fungal meningitis has been associated with frequent treatment related complications, neurological sequelae and a high rate of mortality [4]. It often requires close monitoring and counselling for treatment adherence due to high rates of relapse associated with early termination of treatment.

Etiology

The most frequently encountered pathogen that causes fungal meningitis is Cryptococcus neoformans. It commonly inhabits the soil and is widely found in the environment. Infection occurs through inhalation of air-borne spores. Interestingly, the inhalation of spores does not result in an infection in healthy hosts, rather only those individuals who are immunocompromised, as they are unable to prevent the survival and growth of the fungal spores [1]. C. neoformans infection can present as cutaneous lesions, pulmonary involvement and central nervous system (CNS) disease, including meningitis [2].

Epidemiology

C. neoformans is frequent fungal cause of meningitis in immunocompromised hosts. In Africa, it is one of the more common causes of meningitis in adults. Likewise, certain fungal pathogens are endemic to specific parts of United States. For instance, Histoplasma capsulatum is found individuals with a history of contact with bat and bird droppings, typically in Midwestern part of United States. On the other hand, Coccidioides infection, also known as valley fever, is more prevalent in the Southwest region and usually is found in Filipinos, African Americans, immunocompromised hosts and women in third trimester of pregnancy.

Sex distribution
Age distribution

Pathophysiology

The blood-brain barrier formed by meninges protects the brain from the components of immune system in the blood. In situations where the blood-brain barrier is disrupted, such as meningitis, pathogens can disseminate to the brain and may spread rapidly due to partial isolation from the immune system. As the body develops an immune response to the infection, there is inflow of fluid, white blood cells (WBCs) and other inflammatory mediators due to the increased permeability of blood vessels in the meninges and brain. This may lead to cerebral edema that will lead to symptomatic worsening of the patient due to diminished blood flow to various parts of the brain [3].

Fungal meningitis is a non-contagious disease. It may occur due to hematogenous dissemination or by contiguous spread from a local infection. Medications such as steroids, anti-TNF (tumor necrosis factor) agents and those prescribed status-post organ transplantation, are known to weaken the immune system and lead to an increased risk for developing fungal meningitis.

Cryptococcosis occurs due to inhalation of soil that is contaminated with bird droppings. Histoplasma is prevalent in places like caves with bat and bird droppings, typically in the Ohio and Mississippi river valleys. Blastomyces is commonly found in soil that has decaying organic matter, and is mostly prevalent in the northern Midwest region of United States. Coccidioides is endemic to Southwest United States, along with certain parts of South and Central Americas. Candidiasis is usually acquired in an inpatient setting. The route of transmission for most fungal infections is usually thorough inhalation of spores. Meningitis occurs when the fungal infection spreads to the brain.

Prevention

Avoidance of the specific environments that are most likely to have fungal spores is the best way to prevent infection. Immunocompromised individuals should be advised to avoid dusty environments, digging activities and bird droppings, especially if they dwell in a region with prevalence of Histoplasma, Blastomyces or Coccidioides.

Summary

Meningitis is defined as a clinical syndrome that involves inflammation of the meninges. Fungal meningitis occurs usually due to dissemination of a hematogenous fungal infection to the spinal cord. It is a rare cause of meningitis and frequently occurs in immunocompromised states such as cancer and HIV infection. 

Patient Information

Fungal meningitis is a rare disease. It occurs due to spread of a fungus from the blood to the brain and spinal cord. The clinical signs and symptoms that you may experience are similar to those from meningitis due to any other cause. These include headache, nausea, vomiting, stiffness of the neck, fever and inability to tolerate bright light. Unlike several other forms of meningitis, fungal meningitis is a non-contagious disease and occurs only if the infection enters the blood or gains direct access to the brain and spinal cord from a nidus close to these organs. The treatment for fungal meningitis involves the use of high dose anti-fungal drugs, that are given intravenously for several months. The duration of receiving the treatment, however, varies depending on how good your immune system is working and the type of fungus causing your condition.

References

Article

  1. Meningitis Research Foundation. (2003). About the diseases - Fungal Last accessed, Meningitis Research Foundation. 20/3/03. www.meningitis.org/sect5/subsect10.
  2. Cryptococcosis, Mycology Online. Cryptococcosis, University of Adelaide Australia. 2003.
  3. Berkhout B. Infectious diseases of the nervous system: pathogenesis and worldwide impact. IDrugs. 2008 Nov. 11(11):791-5.
  4. Greenberg DA, Aminoff MJ, Simon RP. Chapter 4. Confusional States. In: Greenberg DA, Aminoff MJ, Simon RP, eds. Clinical Neurology. 8th ed. New York: McGraw-Hill; 2012.
  5. Fungal Meningitis. Centers for Disease Control and Prevention. 2012. Available at: http://www.cdc.gov/meningitis/fungal.html. 
  6. Roos KL, Tyler KL. Chapter 381. Meningitis, Encephalitis, Brain Abscess, and Empyema. In: Longo DL, Fauci AS, Kasper DL, Hauser SL, Jameson JL, Loscalzo J, eds. Harrison's Principles of Internal Medicine. 18th ed. New York: McGraw-Hill; 2012.
  7. Koroshetz WJ. Chapter 382. Chronic and Recurrent Meningitis. In: Longo DL, Fauci AS, Kasper DL, Hauser SL, Jameson JL, Loscalzo J, eds. Harrison's Principles of Internal Medicine. 18th ed. New York: McGraw-Hill; 2012.
  8. Sloan D, Dlamini S, Paul N, Dedicoat M. Treatment of acute cryptococcal meningitis in HIV infected adults, with an emphasis on resource-limited settings. Cochrane Database Syst Rev. 2008 Oct 8. CD005647.
  9. Multistate Fungal Meningitis Outbreak Investigation. Centers for Disease Control and Prevention. 2012. Available at: http://www.cdc.gov/hai/outbreaks/meningitis.html. 

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Last updated: 2019-07-11 21:38